LEPTINT1DM · Unraveling the mechanism underlying the anti-diabetic action of leptin
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2012-12-01 → 2016-11-30
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
Лептинът и неговото действие върху специфични неврони (POMC) в мозъка на мишки с диабет тип 1 се анализират, за да се види как се понижава кръвната захар. Разбирането на тези механизми помага за откриване на нови цели за подобряване на грижата при диабет.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Unraveling the mechanism underlying the anti-diabetic action of leptin
Summary description of the project objectives: The main objective of the project is to determine whether leptin action on POMC neurons is required and/or sufficient for leptin’s anti-type 1 diabetic action in mice. Description of the work: To determine whether leptin action on POMC neurons is required and/or sufficient for leptin’s anti-type 1 diabetic action in mice, we generated mice lacking or expressing leptin receptors only in POMC neurons. Pancreatic insulin-producing beta-cells were destroyed rendering these mutants type 1 diabetic. Intracranial administration of leptin was then achieved and clinical symptoms of type 1 diabetes monitored over time. Description of the main results achieved: The hyperglycemia-lowering action of leptin administration was partially blunted in type 1 diabetic mice lacking leptin receptors only in POMC neurons. On the other hand, the hyperglycemia-lowering action of leptin administration was completely abolished in type 1 diabetic mice expressing leptin receptors only in POMC neurons. Expected final results and their potential impact and use (including the socio-economic impact and the wider societal implications of the project so far): Leptin receptors on POMC neurons play a minor role for leptin’s anti-type 1 diabetic action. Thus leptin action on other non-POMC neurons exerts a major role for leptin’s anti-type 1 diabetic effect. Understanding the neuronal and molecular mechanisms underlying leptin action in type 1 diabetes will identify new molecular targets for counteracting the metabolic dysfunctions caused by insulin deficiency. Hence, these studies have the potential to significantly improve diabetes care.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Type 1 diabetes mellitus (T1DM) is caused by pancreatic β-cell loss. The sole life-saving intervention available to the millions affected by T1DM is insulin therapy. Unfortunately, this therapy does not restore normal metabolic homeostasis and as a result the life-expectancy and -quality of T1DM people is worse than the ones of normal subjects. In part, this is due to challenging morbidities of T1DM, as for example heart disease and hypoglycemia, both of which are thought to be caused by insulin therapy itself. Indeed, owing to insulin’s lipogenic actions, this treatment likely contributes to the ectopic lipid deposition (i.e.: in non-adipose tissues) and extremely high incidence of coronary artery disease seen in T1DM subjects. Also, due to insulin’s potent, fast-acting, glycemia-lowering action, this therapy significantly increases the risk of hypoglycemia; a disabling and life threatening event. Because insulin therapy does not restore metabolic homeostasis, better anti-T1DM intervention is urgently needed. Recent findings in rodents strongly indicate that administration of leptin (a slow-acting, glycemia-lowering hormone) reverses the lethal consequences and many of the metabolic defects caused by insulin deficiency. Because leptin exerts lipolytic action and does not cause hypoglycemia, this hormone represents an attractive alternative and/or adjuvant to current T1DM therapy. Yet, the mechanism underlying leptin’s anti-T1DM action is unknown. Here, the hypothesis that hypothalamic neurons mediate leptin’s anti-T1DM action will be directly tested by assessing the efficacy of leptin therapy in T1DM mice lacking or expressing leptin receptor only in specific hypothalamic neurons. Results from these studies will establish the mechanism underlying leptin’s anti-T1DM action and hence bring us closer to develop better anti-T1DM strategies without the risks of hypoglycemia and cardiovascular disease.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITE DE GENEVE · GeneveКоординаторШвейцария
Връзки
Данни: CORDIS, © Европейски съюз